title: Chlorthalidone reduces cardiovascular events compared with hydrochlorothiazide: a retrospective cohort analysis.
abstract: There is significant controversy around whether chlorthalidone (CTD) is superior to hydrochlorothiazide (HCTZ) in hypertension management. The objective of this analysis was to evaluate the effects of CTD compared with HCTZ on cardiovascular event (CVE) rates. We performed a retrospective observational cohort study from the Multiple Risk Factor Intervention Trial data set from the National Heart, Lung, and Blood Institute. The Multiple Risk Factor Intervention Trial was a cardiovascular primary prevention trial where participants were men 35 to 57 years of age enrolled and followed beginning in 1973. CVEs were measured yearly, and time to event was assessed by Cox regression. Systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, potassium, glucose, and uric acid were measured yearly. The difference between groups was evaluated by repeated-measures mixed modeling, and each model was adjusted for predictors of each variable. CVEs were significantly lower in those on CTD (adjusted hazard ratio: 0.51 [95% CI: 0.43 to 0.61]; P<0.0001) and on HCTZ (adjusted hazard ratio: 0.65 [95% CI: 0.55 to 0.75]; P<0.0001) compared with those who took neither drug. When comparing the 2 drugs, CTD had significantly fewer CVEs compared with HCTZ (P=0.0016). CTD displayed significantly lower SBP (P<0.0001), lower total cholesterol (P<0.0001), lower low-density lipoprotein cholesterol (P=0.0009), lower potassium (P=0.0003), and higher uric acid (P<0.0001) over time compared with HCTZ. In conclusion, both HCTZ and CTD reduce CVEs compared with neither drug. When comparing both drugs, CTD reduces CVEs more than HCTZ, suggesting that CTD may be the preferred thiazide-type diuretic for hypertension in patients at high risk of CVEs.
authors.affiliation: University of Michigan Health System, B2D301 SPC 5008, 1500 East Medical Center Dr, Ann Arbor, MI 48109-5008, USA. mdorsch@med.umich.edu
authors.forename: Michael P
authors.initials: MP
authors.lastname: Dorsch
authors.forename: Brenda W
authors.initials: BW
authors.lastname: Gillespie
authors.forename: Steven R
authors.initials: SR
authors.lastname: Erickson
authors.forename: Barry E
authors.initials: BE
authors.lastname: Bleske
authors.forename: Alan B
authors.initials: AB
authors.lastname: Weder
mesh_terms: D000328:Adult; D000787:Angina Pectoris / Q000209:etiology / Q000517:prevention & control; D000959:Antihypertensive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D002752:Chlorthalidone / Q000009:adverse effects* / Q000627:therapeutic use; D002784:Cholesterol / Q000097:blood; D006333:Heart Failure / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D006852:Hydrochlorothiazide / Q000009:adverse effects* / Q000627:therapeutic use; D006973:Hypertension / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000517:prevention & control; D011188:Potassium / Q000097:blood; D012044:Regression Analysis; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000517:prevention & control; D014527:Uric Acid / Q000097:blood
chemical_list: D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D014527:Uric Acid; D002784:Cholesterol; D002752:Chlorthalidone; D011188:Potassium